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Novel Antimicrobial Peptide "Octoprohibitin" against Multidrug Resistant Acinetobacter baumannii

E H T Thulshan Jayathilaka1, Dinusha C Rajapaksha1, Chamilani Nikapitiya1

  • 1College of Veterinary Medicine and Research Institute of Veterinary Medicine, Chungnam National University, Yuseong-gu, Daejeon 34134, Korea.

Pharmaceuticals (Basel, Switzerland)
|August 26, 2022
PubMed

Insights

Octoprohibitin, a synthetic antimicrobial peptide, effectively combats multidrug-resistant Acinetobacter baumannii by disrupting bacterial membranes and DNA. This peptide also inhibits biofilm formation and shows promise in treating infections in zebrafish models with low toxicity.

Area of Science:

  • Microbiology
  • Peptide Science
  • Drug Discovery

Background:

  • Multidrug-resistant (MDR) Acinetobacter baumannii poses a significant threat due to limited treatment options.
  • Antimicrobial peptides (AMPs) represent a promising alternative to conventional antibiotics.

Purpose of the Study:

  • To evaluate the antibacterial and antibiofilm activity of octoprohibitin, a synthetic AMP derived from Octopus minor.
  • To investigate the mechanism of action of octoprohibitin against MDR A. baumannii.
  • To assess the in vivo efficacy and safety of octoprohibitin.

Main Methods:

  • Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) assays.
  • Time-kill kinetics, bacterial viability, and morphological/ultrastructural analyses.
  • Propidium iodide-fluorescein diacetate (PI-FDA) and H2DCFDA staining for membrane permeability and ROS generation.
  • Agarose gel electrophoresis for DNA-binding.
  • Biofilm inhibition and eradication assays (MBIC, MBEC).
  • Cytotoxicity and hemolysis assays.
  • In vivo efficacy study in an A. baumannii-infected zebrafish model.

Main Results:

  • Octoprohibitin demonstrated potent activity against MDR A. baumannii (MIC: 200 µg/mL, MBC: 400 µg/mL).
  • It induced membrane permeability alterations, reactive oxygen species (ROS) generation, and DNA binding.
  • Effective inhibition and eradication of A. baumannii biofilms were observed (MBIC: 1000 µg/mL, MBEC: 1460 µg/mL).
  • Octoprohibitin exhibited low cytotoxicity and no hemolysis at effective concentrations.
  • In vivo studies showed significant survival improvement (46.6%) and reduced pathological signs in infected zebrafish.

Conclusions:

  • Octoprohibitin is a potent antibacterial agent against MDR A. baumannii.
  • Its mechanism involves membrane disruption, ROS generation, and DNA binding.
  • Octoprohibitin also possesses significant antibiofilm properties.
  • The peptide demonstrates a favorable safety profile and in vivo efficacy, suggesting its potential as a therapeutic agent.
Keywords:
Acinetobacter baumanniiantimicrobial peptidebiofilm eradicationbiofilm inhibitionmultidrug resistanceoctoprohibitinzebrafish

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